Fig. 8: Model of myocyte fusion regulation by PP2A-Bδ.
From: Dephosphorylation of HDAC4 by PP2A-Bδ unravels a new role for the HDAC4/MEF2 axis in myoblast fusion
Activation of MEF2-dependent transcription is under the control of reversible phosphorylation of HDAC4 by myogenic kinases and opposing PP2A-Bδ. In proliferating myoblasts, phosphorylation levels of HDAC4 are low because myogenic kinases are inactive. At the onset of differentiation, extracellular myogenic signals activate HDAC4 kinases. Dephosphorylation by PP2A-Bδ is prevented due to high levels of I1/I2PP2A. HDAC4 becomes highly phosphorylated, which promotes its dissociation from MEF2 and activation of MEF2-regulated genes, including effectors of the differentiation programs as well as fusion factors (e.g. ArgBP2). As myocytes complete differentiation, myogenic kinases are inactivated and I1/I2-PP2A levels drop. This allows PP2A-Bδ to efficiently dephosphorylate HDAC4, which reinstates repression over MEF2. Shutdown of MEF2-dependent transcription by PP2A-Bδ terminates the genetic differentiation programs and prevents excessive accumulation of the fusion regulators allowing the morphogenic events required for proper myoblast fusion to occur
